Efficient Dendritic Cell Priming of T Lymphocytes Depends on the Extracellular Matrix Protein Mindin

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Aug 19

PMID 16917498

Citations 28

Authors

Hong Li

Tim Oliver

Wei Jia

You-Wen He

Affiliations

Soon will be listed here.

Abstract

Rho guanosine triphosphatases (GTPases) regulate multiple aspects of dendritic cell (DC) function, but what regulates the expression of Rho GTPases in DCs is unknown. Here, we show that the extracellular matrix protein mindin regulates the expression of Rho GTPases in DCs. Mindin(-/-) mice displayed defective CD4+ T-cell priming and impaired humoral immune responses to T-dependent antigens. Mindin(-/-) DCs had reduced expression of Rac1/2 and impaired priming capacity owing to inefficient engagement with T lymphocytes. Ectopic Rac1 expression restored the priming capability of Mindin(-/-) DCs. Furthermore, we show that DC adhesion to mindin matrix was blocked by antibodies to alpha4, alpha5 and beta1 integrins. DCs lacking beta1 integrin had reduced adhesion to mindin matrix, decreased expression of Rac1/2 and impaired priming capacity. These results suggest that mindin-integrin interactions play a key role in regulating Rho GTPase expression in DCs and DC priming of T lymphocytes.

Citing Articles

Comprehensive analysis of the oncogenic and immunological role of SPON2 in human tumors.

Tang J, Huang Q, Li X, Gu S Medicine (Baltimore). 2023; 102(37):e35122.

PMID: 37713832 PMC: 10508437. DOI: 10.1097/MD.0000000000035122.

A Wrinkle in TIME: How Changes in the Aging ECM Drive the Remodeling of the Tumor Immune Microenvironment.

Harper E, Weeraratna A Cancer Discov. 2023; 13(9):1973-1981.

PMID: 37671471 PMC: 10654931. DOI: 10.1158/2159-8290.CD-23-0505.

MACC1-induced migration in tumors: Current state and perspective.

Hohmann T, Hohmann U, Dehghani F Front Oncol. 2023; 13:1165676.

PMID: 37051546 PMC: 10084939. DOI: 10.3389/fonc.2023.1165676.

Mindin Activates Autophagy for Lipid Utilization and Facilitates White Spot Syndrome Virus Infection in Shrimp.

Gao J, Song Y, Wang H, Zhao B, Wang X mBio. 2023; 14(2):e0291922.

PMID: 36779788 PMC: 10127999. DOI: 10.1128/mbio.02919-22.

Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC.

Huang C, Ou R, Chen X, Zhang Y, Li J, Liang Y J Exp Clin Cancer Res. 2021; 40(1):304.

PMID: 34583750 PMC: 8477524. DOI: 10.1186/s13046-021-02108-0.

References

Pribila J, Itano A, Mueller K, Shimizu Y . The alpha 1 beta 1 and alpha E beta 7 integrins define a subset of dendritic cells in peripheral lymph nodes with unique adhesive and antigen uptake properties. J Immunol. 2003; 172(1):282-91. DOI: 10.4049/jimmunol.172.1.282. View

Jia W, Li H, He Y . The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment. Blood. 2005; 106(12):3854-9. PMC: 1895097. DOI: 10.1182/blood-2005-04-1658. View

Benvenuti F, Hugues S, Walmsley M, Ruf S, Fetler L, Popoff M . Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming. Science. 2004; 305(5687):1150-3. DOI: 10.1126/science.1099159. View

Miller M, Safrina O, Parker I, Cahalan M . Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J Exp Med. 2004; 200(7):847-56. PMC: 2213293. DOI: 10.1084/jem.20041236. View

Zhang M, Tang H, Guo Z, An H, Zhu X, Song W . Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol. 2004; 5(11):1124-33. DOI: 10.1038/ni1130. View

Klar A, Baldassare M, Jessell T . F-spondin: a gene expressed at high levels in the floor plate encodes a secreted protein that promotes neural cell adhesion and neurite extension. Cell. 1992; 69(1):95-110. DOI: 10.1016/0092-8674(92)90121-r. View

Liakka K . Distribution of the extracellular matrix proteins tenascin, fibronectin, and vitronectin in fetal, infant, and adult human spleens. J Histochem Cytochem. 1992; 40(8):1203-10. DOI: 10.1177/40.8.1377736. View

Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S . Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992; 176(6):1693-702. PMC: 2119469. DOI: 10.1084/jem.176.6.1693. View

Kilshaw P . Expression of the mucosal T cell integrin alpha M290 beta 7 by a major subpopulation of dendritic cells in mice. Eur J Immunol. 1993; 23(12):3365-8. DOI: 10.1002/eji.1830231246. View

10.

Kuhn R, Schwenk F, Aguet M, Rajewsky K . Inducible gene targeting in mice. Science. 1995; 269(5229):1427-9. DOI: 10.1126/science.7660125. View

11.

Del Pozo M, PRICE L, Alderson N, Ren X, Schwartz M . Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. EMBO J. 2000; 19(9):2008-14. PMC: 305684. DOI: 10.1093/emboj/19.9.2008. View

12.

Plow E, Haas T, Zhang L, Loftus J, Smith J . Ligand binding to integrins. J Biol Chem. 2000; 275(29):21785-8. DOI: 10.1074/jbc.R000003200. View

13.

West M, Prescott A, Eskelinen E, Ridley A, Watts C . Rac is required for constitutive macropinocytosis by dendritic cells but does not control its downregulation. Curr Biol. 2000; 10(14):839-48. DOI: 10.1016/s0960-9822(00)00595-9. View

14.

GARRETT W, Chen L, Kroschewski R, Ebersold M, Turley S, Trombetta S . Developmental control of endocytosis in dendritic cells by Cdc42. Cell. 2000; 102(3):325-34. DOI: 10.1016/s0092-8674(00)00038-6. View

15.

Raghavan S, Bauer C, Mundschau G, Li Q, Fuchs E . Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination. J Cell Biol. 2000; 150(5):1149-60. PMC: 2175239. DOI: 10.1083/jcb.150.5.1149. View

16.

Wu X, Jiang N, Fang Y, Xu C, Mao D, Singh J . Impaired affinity maturation in Cr2-/- mice is rescued by adjuvants without improvement in germinal center development. J Immunol. 2000; 165(6):3119-27. DOI: 10.4049/jimmunol.165.6.3119. View

17.

Puig-Kroger A, Sanz-Rodriguez F, Longo N, Sanchez-Mateos P, Botella L, Teixido J . Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells. J Immunol. 2000; 165(8):4338-45. DOI: 10.4049/jimmunol.165.8.4338. View

18.

Kamath A, Pooley J, OKeeffe M, Vremec D, Zhan Y, Lew A . The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J Immunol. 2000; 165(12):6762-70. DOI: 10.4049/jimmunol.165.12.6762. View

19.

del Pozo M, Kiosses W, Alderson N, Meller N, Hahn K, Schwartz M . Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nat Cell Biol. 2002; 4(3):232-9. DOI: 10.1038/ncb759. View

20.

Shortman K, Liu Y . Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002; 2(3):151-61. DOI: 10.1038/nri746. View